Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 2024 Rohrhofer et al

[jnmaciuch]

Whether all mast cells develop initially in bone marrow and travel as basophils or from local division is probably a continuing issue of debate, just as it is for macrophages.

Tangential to the thread but there have been quite a few fate mapping studies in mice showing that there are self-renewing tissue resident macrophage populations established in the fetus. They get supplemented by CCR2+ mono-derived macrophages and there’s some indications that the circulation-derived ones can take over the tissue resident niche if it’s completely depleted. But they are distinct even at the transcriptional level

 

[Jonathan Edwards]

I just looked on Wikipedia, and it suggests that was how it was previously understood, but is different now:

That doesn't make sense to me. What do all the basophils turn into then? Are they just there to entertain haematology technicians?

There is a huge amount of folklore around this stuff, as you know. The folklore is always trendier so it gets repeated by things like WikiP. They made a dog's breakfast of macrophage subsets. I suspect this is the same.

 

[Jonathan Edwards]

Tangential to the thread but there have been quite a few fate mapping studies in mice showing that there are self-renewing tissue resident macrophage populations established in the fetus.

But that is mice.
Fifty years on I am not convinced anyone actually knows the answer to this. Eric Topol recently said that we had suddenly realised that monnocytes get into aging human brain after all. The merry go round goes round.

 

[jnmaciuch]

But that is mice.
Fifty years on I am not convinced anyone actually knows the answer to this. Eric Topol recently said that we had suddenly realised that monnocytes get into aging human brain after all. The merry go round goes round.

you may have missed a paper or two on non-viable human embryos

 

[Hutan]

As chronic mast cell activation is difficult to determine, due to the acute nature and short half-life of the major mediators tryptase and histamine [24], we aimed to measure the serum levels of ECP and EDN.

ECP = eosinophil cationic protein
EDN = eosinophil-derived neurotoxin

So these are eosinophil proteins that they assume would also be increased in case of chronic mast cell activation.

It does seem possible that this measuring of the eosinophil proteins when you want to know about mast cell activation is a bit like the drunk person looking for their car keys at night under the street lamp, even though they may well have left them up the road a bit in the dark.

As best as I can work out , the eosinophils and the mast cells are often activated together, and raised ECP would be a sign of inflammation. So, if the ECP was increased in ME/CFS, that could be suggestive of mast cells being activated, but it's certainly not a smoking gun.

(Just to remind ourselves, in this study, there were no differences in ECP levels between the ME/CFS and control cohorts. So, no sign of the eosinophils doing anything odd, making it less likely that the mast cells are doing anything odd either.)


Analysing the eosinophil cationic protein - a clue to the function of the eosinophil granulocyte, 2011

Since the discovery of ECP in 1977 [8] it has been used and evaluated as a biomarker to assess activity in various inflammatory diseases.

So, ECP was certainly a good thing to measure, and the normal level in ME/CFS should have been noteworthy, discussion worthy, for what it suggests is not going on. That is, probably, as far as I can see, not an inflammatory situation, probably not an eosinophil disease and probably not mast cell activation, probably not some sorts of infection, probably not an allergy.

I get the feeling that this useful finding was ignored, because it did not fit the preconceived ideas of the authors about what ME/CFS is. It wasn't reported in the abstract. All that the paper reported was

The measurement of ECP did not reveal differences between the test groups of the study cohort and thus is not shown.

The actual levels aren't even reported in the table A2 where other non-significant the results are reported. The null finding is not discussed in the Discussion.

I haven't looked into the other eosinophil protein measured - EDN (for which there were also no statistically different results)

 

[Jonathan Edwards]

you may have missed a paper or two on non-viable human embryos

I can't see how observations on embryos can tell us anything definitve either.

But the main point is that mast cells are not eosinophils.